Polyfluoroalkoxy-substituted aromatic carboxylic acids

ABSTRACT

Acyl halides, esters, amides, hydrazides and salts as well as the acid form derived from aromatic acids substituted by polyfluoroalkoxy groups. These compounds are valuable as synthetic intermediates in the preparation of physiologically active compounds.

United States Patent [191 Mendel Dec. 2, 1975POLYFLUOROALKOXY-SUBSTITUTED AROMATIC CARBOXYLIC ACIDS Arthur Mendel,Vadnais Heights, Minn.

Inventor:

Riker Laboratories, Inc., Northridge, Calif.

Filed: Apr. 9, 1973 Appl. No.2 349,237

Related U.S. Application Data Division of Ser. No. 57,350, July 22,1970, Pat. No. 3,766,247.

Assignee:

U.S. Cl 260/544 M; 424/309; 424/324 Int. Cl C07C 65/08; CO7C 63/02;

CO7C 65/14 Field of Search 260/544 D, 544 F References Cited UNITEDSTATES PATENTS 3/l973 Mendel et al 260/544 D FOREIGN PATENTS ORAPPLICATIONS 1.185.096 12/1964 Germany 260/544 D Primary ExaminerJamesA. Patten Assistant ExaminerRichard D. Kelly Attorney, Agent, orFirm-Alexander, Sell, Steldt & DeLal-lunt [57] ABSTRACT 7 Claims, N0Drawings POLYFLUOROALKOXY-SUBSTITUTED AROMATIC CARBOXYLIC ACIDS This isa division of application Ser. No. 57,350 filed July 22, 1970, now US.Pat. No. 3,766,247.

DETAILED DESCRIPTION This invention relates topolyfluoroalkoxy-substituted aromatic carboxylic acids and amides,esters, acyl halides, hydrazides and salts derived therefrom. Thesecompounds are useful as synthetic intermediates in the preparation ofphysiologically active compounds, such as local anesthetics andantiarrhythmics.

A preferred class of compounds of the invention are those having theformula:

wherein X is amino (NH 2-haloethylamino, hydrazino (NHNl-l alkoxy (ORwherein R is alkyl or CH R,), halogen (selected from fluorine, chlorineand bromine), hydroxy or OM (wherein M is a metal ion), Ar is anaromatic carbocyclic system of 6 to 10 carbon atoms, each R is afluorocarbon group containing from 1 to 3 carbon atoms and n'is l to 4.The complete fluorocarbon group (R,) can be a fully or partiallyfluorinated alkyl group having a straight or branched structure. Therecan be no more than one hydrogen atom on any carbon atom and two carbonatoms in the R, group can be linked together by an oxygen atom. Thus, inaddition to the optional oxygen atom, R, can

contain only carbon, fluorine and hydrogen; A pre-' ferred class of thecompounds of the invention is made up of those compounds in which R is CF Y, wherein m is 1-3 and Y is hydrogen or fluorine.

A particularly preferred subclass of the compounds are those in which Aris anaphthalene nucleus and n is one. These compounds are particularlyuseful for the preparation of local anesthetics having activity of longduration. When X is 2-haloethylamino the halogen is chlorine or bromine.

A second preferred subclass consists of compounds in which Ar is abenzene nucleus and n is one or two. These compounds are particularlyuseful for the preparation of antiarrhythmics of high potency.

Generally, compounds of the invention wherein R, is CF are mostpreferred;

The metal ions (M) in the salts of the invention are preferably alkalimetals (such as sodium and potassium), alkaline earths (such asmagnesium and calcium), aluminum and'the like.

Compounds of the invention wherein X is amino, -OR, halogen, hydrazino,hydroxy or OM are readily interconverted to one another by well-knownsynthetic procedures. g

The compounds of Formulal, wherein X is OR, can be produced by reactinga compound of Formula II with an alkylating ester, for example afluoroalkyl trifluoromethanesulfonate of Formula III, as shown in thefollowing equation:

Equation 1 II III nCF SO H wherein R is alkyl and Ar, R, and n are asdefined hereinabove.

This reaction is carried out in the presence of sodium carbonate orpotassium bicarbonate in an inert solvent such as acetone. Alternativelycompounds of Formula II wherein R is hydrogen may be reacted with n 1moles of compounds of Formula Ill to give compounds of Formula I whereinX is OCH R;.

The esters of Formula I may be hydrolyzed to the free acid (Formula I, XOH).

Compounds of Formula I wherein X is halogen are conveniently prepared byrefluxing the corresponding esters of Formula I (compounds wherein X isOR) with an excess of thionyl chloride in the presence of a small amountof dimethylformamide. Other conventional methods for the synthesis ofacyl halides may also be useful.

Compounds of Formula I wherein DX is amino (that is, amides) areconveniently prepared from compounds of Formula I wherein X is halogenby reaction with ammonia, from esters of Formula I by reaction withconcentrated ammonium hydroxide and other well-known synthetic methods.

Compounds of Formula I where X is hydrazino are most commonly preparedby treating the ester or acyl halide of Formula I with 40 per centaqueous hydrazine hydrate solution.

Compounds of Formula I wherein X is OH (that is, acids) are prepared byhydrolysis of compounds of Formula I wherein X is halogen, amino,hydrazino or OR, or by acidification of compounds of Formula I wherein Xis OM.

Compounds of Formula I wherein X is -OM are most conveniently preparedby reaction of acids of Formula l with metal hydroxides or alkoxides,but may also be prepared by hydrolysis of esters, amides, hydrazides andacyl halides of Formula I with metal hydroxides and alkoxides underconditions which modify the rates of these sometimes strongly exothermichydrolyses.

Compounds of the invention wherein X is Z-haloethylamino are prepared byreaction of compounds of the invention wherein X is chlorine or brominewith ethyleneimine followed by treatment with isopropanolic hydrogenhalide to give the desired compound.

The compounds of this invention are converted directly to usefulproducts such as physiologically active compounds, or indirectly byconversion to other compounds of the invention more suitable as directintermediates to useful physiologically active compounds. Thus, acids ofFormula I can be reacted with Z-dialkylaminoalkyl halides (or saltsthereof) such as 2-(diethylamino)ethyl bromide and its hydrochloridesalt in the presence of an acid acceptor, such as potassium bicarbonateor sodium carbonate in an inert solvent such as toluene or benzene togive 2-dialkylaminoalkylene esters of fluoroalkoxy-substituted aromaticacids. Such compounds are also prepared by transesterification of estersof Formula I with a dialkylaminoalkanol such as 2-diethylaminoethanol.

The 2-dialkylaminoalkylene esters of fluoroalkoxysubstituted aromaticacids are active local anesthetics when tested by well-known screeningmethods, and in particular by the corneal reflex test on rabbitsdescribed in detail by Luduena and Hoppe, J. Pharm. Exptl. Therap.,104240, 1952. Compounds active as local anesthetics prepared from thecompounds of the present invention include:

2-(diethylamino)ethyl 2-(2,2,2 trifluoroethoxy)-2 naphthoate2-(diethylamino)ethyl 2,5 -di-(2,2.Z-tnifluoroethoxy)-benzoate2-(diethylamino)ethyl l-(2,2,2-trifluoroethoxy)-2 naphthoate andpharmaceutically acceptable salts of these compounds.

The compounds of the invention can also be utilized to preparephysiologically active antiarrhythmic compounds by reaction of compoundsof Formula 1 wherein X is halogen with a 2-(dialkylamino)alkylamine inan inert solvent, such as benzene, toluene or diethyl ether.Alternatively compounds of Formula 1 wherein X is OR may be reacted with2-(dialkyamino)alkylamines. Compounds of the invention wherein X is 2-haloethylamino are converted to active antiarrhythmics by reaction withappropriate secondary amines. The N-(2-dialkylaminoalkylene) amides ofpolyfluoroalkoxy-substituted aryl (dialkylamino)alkylw mines. acidswhich are prepared from the compounds of the present invention areactive antiarrhythmies ac cording to a wellknown screening methoddescribed in detail by Lawson in J. Pharm. Expt. Therap. 160:22, 1968.The activity is manifested in the ability to block chloroform-inducedventricular fibrillation in mice. Compounds particularly active asantiarrhythmics prepared from the compounds of the present inventioninclude:

'mole), 2,2,2-trifluoroethyl trifluoromethanesulfonate (13.9 g. 0.06mole), anhydrous potassium carbonate (13.8 g., 0.1 mole) and acetone(150 ml.) is heated under reflux with efficient stirring for 3 days. Theprod uct is filtered and the filtrate is concentrated to a-small'EXAMPLE 2 Preparation of Methyl l-(2,2.2-Trifluoroethoxy)-2- NaphthoateA mixture containing 20.2 g. (0.1 mole) of methyl lhydroxy-Z-naphthoate.29 g. (0.125 mole) of-2 ,2,2- trifluoroethyl trifluoromethanesulfonate,20 g. (0.2 mole) of anhydrous potassium bicarbonate and 200 ml. of dryacetone is refluxed for three days. Acetone is removed by distillation(steam bath). The residue is cooled and diluted with water. Theresulting white solid is collected by filtration and washed successivelywith cold dilute sodium hydroxide solution and water. The solid isfurther purified by several recrystallizations from aqueous alcoholfollowed by sublimation, (oil bath, 60-75/0.2 mm. Hg.) to give whitesolid, mp. 69.5-70.5.

hy n hy- 4Z J- h Y Analysis: Calculated for c n r o c, 59.2; H, 3.9;

benlmlde F, 20.0 Found: c, 58.9; 1-1, 4.0; F. 21.1 ly y Z Y Additionalcompounds of the invention wherein X is benz'flmlde OR are preparedaccording to the procedures de-N'(z'dlefllylammoethyn'44ztzzmfluoroglhoxyy scribed in Examples 1 and 2and are listed in Table l.

benzamide 35 T l N-(2-diethylaminoethyl)-2,4-di-(2.2,2-trifluoroe- ABLEthoxy)-benzamide Example Melting PointN-(2-diethylaminoethyl)-2,5-di-(2.2,2-trifluoroe- Cmnpound C)thoxy)-benzamide 3 methyl 57.5-59 7 2- 4()3-(2,2.2-trifluorocthoxy)benzoate N (2 diethylamlnoethyl) 2,6 d1 (...2,trifluoroe 4 mcthy 59-5405 thoxy)-benzam1de4-(2.2,2-trifluoroethoxy)benzoateN-(2-diethylaminoethyl)-3,4-di-(2.2,2-trifluoroe- 5 g y a 2 h W -31 l-41'] UOlOBl OX) enzoate 0 methyl 70.5-71.5 N-( 2-d1ethylam1noethyl)- l2.2.2-tr1fluoroethoxy z 4. zggmfluomethoxy)bcnzoate Z-naphthamide 7methyl 42.44 ..'-d'- 2.22 n h bN-(2-pyroll1d1nylethyl)-3-(2,2,2-tr1fluoroethoxy)-2- 8 5244 phthamid2.6-di-(2.2,2-trifluoroethoxy)benzoate 9 th '1 57-59N-(2-d1ethylam1noethyl)-2,4,6-tr1-(2.2,2-tr1fluoroegladlyzzvuriflumocthoxy)benzoate thoxy)benzam1de 10methyl 81.5-82.5 and pharmaceutically acceptable salts of these com- I 2-23; 86 87 P 3.4,5-tri-(2,2,2-trifluoroethoxy)benzoate The followingexamples will more fully illustrate the methyl 77-77.5 preparation ofthe compositions of the invention. All 3 (z z z n-ifl h 2 h htemperatures in the examples are given in C.

EXAMPLE 1 Compounds of the invention where m and n are I greater thanone are prepared according to the proce- Preparation of Methyl JJ- y)dures described in Examples 1 and 2 utilizing intermezoate diates ofFormula 111 other than 2,2,2-trifluoroethyl tri- A mixture of methyl s ly g-- fluoromethanesulfonate are shown in Table 11.

TABLE 11 Starting Materials Example No. Formula II Formula 111 Product1} methyl Z-hydroxy- 1,1-dihydroperi'iuoromethyl 2-(1,i

benzoate n-propyl trifluorodihydropermethanesulfonatefluoro-npropoxy)benzoa TABLE ll-continued Starting Materials An exampleof preparation of a compound of Formula I wherein X is OCH C F Y isgiven in Example 19.

EXAMPLE 19 Preparation of 2,2',2'-Trifluoroethyl2,5-di-(2,2,2-trifluoroethoxy)benzoate To a stirred refluxing suspensionof 2,5-dihydroxybenzoic acid (88.3 g., 0.573 mole), potassiumbicarbonate (573 g., 5.73 mole) and acetone (2.4 l.) is added dropwise2,2,2-trifluoroethyl trifluoromethane- A sulfonate (564 g., 2.43 mole)in acetone (230 ml.). The

EXAMPLE 20 Using the method of Example 19, 2, 4, 6-trihydroxybenzoicacid is reacted with 2,2,2-trifluoroethyl trifluorqmethanesulfonate togive 2',2',2'-trifluoroethyl 2,4,6-tri-(2,2,2-trifluoroethoxy)benzoate,m.p. 648 to 65.8.

EXAMPLE 21 Preparation of 2-(2,2,2-Trifluoroethoxy)benzoic Acid Methyl2-(2,2.2-trifluoroethoxy)benzoate (8 g., 34.2 mmoles) potassiumhydroxide (3.3 g., 350 mmoles), water (50 ml.) and alcohol (25 ml.) areheated together under reflux for 1.5 hours, and distilled until ca. 25ml. of distillate is removed. The cooled residue is acidified (pH 3) andthe resulting white solid is collected and recrystallized (aqueousalcohol) to give fluffy white solid, m.p. 8586.5 C.

Analysis: Calculated for C H F O C. 49.1; H, 3.2; F, 25.9 Found: C,48.8; H, 3.3; F, 26.2

EXAMPLE 22 Preparation of 1-(2,2,2-Trifluoroethoxy)-2-Naphthoic Acid Amixture of 10 g. (35 mmoles) of methyl l-(2,2,2-trifluoroethoxy)-2-naphthoate, 2.9 g., (42 mmoles) of potassiumhydroxide, 50 ml. of ethanol and 40 ml. of water is refluxed for 1 hour,chilled and acidified. The fluffy precipitate is collected, waterwashed, and airdried. it is purified by recrystallization first fromchloroform and then from aqueous alcohol, m.p. l7l.5-172 C.

Analysis: Calculated for C I-1 1 0 C, 57.8; H, 3.4; F, 21.1 Found: C,57.8; H, 3.6; F, 21.7

Compounds of the invention of Formula I wherein X is OH are obtainedfrom each of the products of Examples 3 through 12 by the methodsdescribed in detail in Examples 21 and 22. Such products are listed inTable III. 5

Compounds of the invention wherein X is OH and m and n are greater thanone are prepared according to he procedures described in Examples 21 and22 and isted in Table IV.

EXAMPLE 43 Preparation of 4-(2,2,2-Trifluoroethoxy)benzamide A solutionof methyl 4-(2,2,2-trifluoroethoxy)-benfluoroethoxy)-benzamideEthyleneimine (2.9 g., 0.068 mole), triethylamine (6.8 g., 0.068 mole)and diethyl ether (250 ml.) are cooled to C. and stirred while adding2,S-di-(2,2,2-trifluoroethoxy)benzoyl chloride (22.8 g., 0.068 mole).The mixture is allowed to warm to room temperature and filtered. Thefiltrate is treated with 6.6 N isopropanolhydrochloric acid mixture andfiltered and the solvent evaporated in vacuo to giveN-(2-chloroethyl)-2,5-di- (2,2,2-trifluoroethoxy)benzamide, m.p. 8788.5C.

Analysis: Calculated for C l-l ClF NO C, 41.5; H, 3.2; N, 3.6 Found: C,41.1; 1-1, 3.2; N, 3.7

EXAMPLE 41 Preparation of 1-(2,2,Z-Trifluoroethoxy)-2-naphthoyl ChlorideA mixture of 10 g. (37 mmoles) of l-(2,2,2-trifluoroethoxy)-2-naphthoicacid, 21.8 ml. (35.7 g., 300 mmoles) of purified thionyl chloride and 3drops of di methylformamide is refluxed for 1 hour. Excess thionylchloride is removed in vacuo at water aspirator pressure while heatingon a steam bath. Last traces of thionyl chloride are removed by vacuumdistillation with added benzene. The product isl-(2,2,2-trifluoroethoxy)-2-naphthoyl chloride according to infraredspectral measurement.

EXAMPLE 42 Preparation of 2,5-Di-(2,2,2-Trifluoroethoxy)benzoyl ChlorideTo 9.4 g. mmoles) of 2,5-di-(2,2,2-trifluoroethoxy)benzoic acid areadded 2 drops of dimethylformamide and 7.2 ml. (11.9 g., 100 mmoles) ofpurified thionyl chloride. The product is refluxed for 3 hours andexcess thionyl chloride is removed in vacuo (steam bath/water aspiratorpressure). Last traces of thionyl chloride are removed by similar vacuumdistillation with added benzene. The product is2,5-di-(2,2,2-trifluoroethoxy)benzoyl chloride according to infraredspectral measurement.

zoate (3 g., 0.013 mole) in methanol (25 ml.) is cooled using a dry-iceacetone bath, and the solution is saturated with anhydrous ammonia, thenheated in a pressure reactor at 1 10 for 10 hours. The methanolicsolution is filtered and the filtrate is evaporated. The residue ischromatographed on neutral aluminaand the early fractions which eluterapidly with ethyl acetate are discarded, methyl ethyl ketone fractionsare discarded and methanol fractions finally give a tan' solid whenevaporated. When recrystallized from ethanol the white solid is found tobe 4-(2,2,2 trifluoroethoxy)- benzamide, m.p. 177l78C.

Analysis: Calculated for C H FQNOQ, C, 49.3; H, 3.7; i

F, 26.0; N, 6.4; Found: c, 49.5; H, 3.8; F, 2 .0; N, 6.4.

EXAMPLE .44

Preparation of 4-(2,2,2-Trifluoroethoxy)benzamide To4-(2,2,2-trifluoroethoxy)benzoic acid (2.2 g.,

0.01 mole) is added thionyl chloride (23.8 g., 0.2 mole) and the mixtureis heated at reflux temperature for two hours. Excess thionyl chlorideis. removed by distillation on a steam bath at water aspirator pressure.Cold concentrated ammonium hydroxide is added in small portions to thecooled 4-(2,2,2-trifldoroethoxy)benzoyl chloride. The white solidproduct is collected by filtration and recrystallized from ethanol, m.p.l77178. Its infrared spectrum is identical' to tha t'of the'product ofExample 43. I

Compounds of the invention of Form'ula 1 wherein X is NH are obtained bythe methods described in detail in Examples 43 and 44. Such products arelisted in Table V.

TABLE V Example Melting Point No. Product (in C.)

45 3-(2,2,2-trifluoroethoxy)benzaniide 14615-1475 463,4-di-(2,2,2-trifluoroethoxy)benzamide1-- 172-173 472,5-di-(2,2.2-trifluoroethoxy)benzamiqle 131-133 483,4.5-tri-(2,2,2-trifluoroethoxy)benzamide 146-147 492-(2,2,Z-trifluoroethoxy)benzamide 143144.5 502,4.6-tri-(2,2,2-trifluoroethoxy)benzamide 12 l l 22 513,5-di-(2.2.2-trifluoroethoxy)benzamidc 127.5-1285 522,6-di-(2,2.2-trifluoroethoxy)benzamide 1 15-1 16 53 2.4-di-(2,2.2-trifluoroethoxy)benzamide -136 9 TABLE V Continued TABLE vllExample Melti g Point Example Melting Point No. Product (in T.) No.Compound (ln C.)

54 QQ- Y) P 169-170 5 63 3,4-di-(2,2,2-trifluoroethoxy)benzoic l29l30.555 l-(2.2,2-trifluoroethoxy)-2-naphthzlmidc 182-1835 acid hydruzide 64 2.5-di-( 2.2.2-trifluoroethoxy )benzoic 89-925 Compounds of the inventionwherein X is NH and m acid hydrazide I 4 18 greater than one areobtained by the methods de- ()5 f' i ZOlC acid hydrazlde scribed inExamples 43 and 44 and are listed in Table 663.5-di-(2,2.2-trifluoroethoxy)benzoic 121-1225 VL acid hydrazide 672.4-di-(2,2,2-trifluoroethoxy)benzoic l l 1.5-1 l2 acid hydrazide TABLEVI 68 3-(2.2.2-trifluoroethoxy)benzoic acid 1235-124 hydrazide ixgmpleStarting Mater Product 69 2,4,6-triifi,fiZ-trfluoroethoxy)benl36-l37201C aCl y I'flZl e 56 2(l,l-dihydroperfluoro-n-2-(1,l-dihydroperfluoro-mp 70 l-(2,2.2-trifluoroethoxy)-2-naphll7-l l9propoxy)be nzoic acid n-propoxy)benzamide thoic acid hydrazide benzoicacld 7l 3-(2,2,Z-trifluoroethoxy)-2-naphl53l55 th 'd h d 'd 57 n-propyl2,5-di-(1,l-dihydroperam y e 2.5-di-( l, 1-dihydroperfluoroisobutoxy)benzamide fluoroisgbutoxy)benzoi acidCompounds of the lnventlon wherein X is hydrazmo 2 (I l 3 t h d m I, 2(l l 3 t h d and m is greater than one are prepared by the methods 53 -ny rope uoro -n y ropern-propoxy)benzoicacid fluoro-n-propoxylbenzamide gigli lfifl fi Examples 61 and 62 and are listed m 594-[2,2-difluoro-2-(tri- 4-[2,2-difluoro-2- I fluoromethoxy)ethoxy]-(trifluorornethoxy)- TABLE VIII benzoic acid ethoxylbenzamide Example 0l-(1,1-dihydroperfluoron- I-(Ll-dihydropmfluoro- No. Starting MaterialProduct butoxy)2-naphthoic acid n-butoxy)-2-naphthamide 72 2-( l,l-dihydroperfluoro-n-propox- 2-( l l -dihydropery)bcnzoic acidfluoro-n-propoxy)- EXAMPLE 6| benzoic acid hydrazide Preparation of2-(2,2,2-Trlfluoroethoxy)benzolc Acid 73 n-propyl 2 5-di.(] .dihy. H did 2,5-di- LI-dihydroper: droperfluoroisobutox- Methyl2-(2,2,2-trifluoroethoxy)benzoate (1.22 g. fluom'sobutoxwbenww and 5.2mmole), ethanol (15 ml.) and 5 ml. Of 95 per cent 742-(l.l,3-trihydroperfluoro'n- 2-(l,l.3-trihydroperhydrazine (4.75 g.,158 mmole) are refluxed for two propflwbenzmc acld 2233;31 :3 hours,cooled, diluted with water 100 ml.) and cooled. hydrazide The whitesolid product, 2-(2,2,2-trifluoroethoxy)ben- 75 -l i fl ifl r4-[2.2-difluo o-2-(trizoic acid hydrazide is recrystallized fromethanol, m.p. hmmethmylbenzmc g fgggf f gy 102 -104 hydrazide Analysis:Calculated for C H F N O C, 46.2; F, 76 Q t p fl g gy f y -..nap OIC aCluoro-nutoxy 24.3; N, 12.0 Found. C, 46.3, F, 25.3, N, 12.0 naphlhoicacid EXAMPLE 62 hydmide Preparation of2,6-Di-(2,2,2-trifluoroethoxy)benzoic EXAMPLE 77 Acid HydrazidePreparation of Sodium 2-(2,2,2-Trifluoroethoxy)ben- Thionyl chloride (l1.9 g., 100 mmole), 2,6-di-(2,2,2- l Trifluoroethoxy)benzoic acid (2.0g., 6.3 mmole) and 13 gg gz g hgf q alcld dlssilvid m e I 0 an e e M anequlmo ar amou n 0 sotwo drops of y f9rm;mldeflare i g to regux diumhydroxide dissolved in a minimum amount of ethtemperatufe and f if at ref P anol and stirred for one hour. The solvent is' removed reactedthlonyl chloride is removed by dlstlllatlon on a 5 by evaporation vacuoto give Sodium steam bath at water aspirator pressure. The resldue lSfluoroethoxy)benzoate dissolved in dry tetrahydrofuran and addeddropwise to Other salts of the invention are readily prepared in an asolution of 95 per cent hydrazine (3.2 g.. lOO mmole) analogolls inethanol (15 ml.). The mixture is allowed to sit overf? f 1 night andevaporate to dryness. The residue is diluted Ompoun 0 e a with water anda white solid collected and purified by g sublimation (l38-l40/0.2 to0.5 mm. Hg.) followed X- -Ar(OCH R,),, l! recrystallization f to give23641142272 wherein X is halogen selected from fluorine, chlorinemfluoroethoxwbenzolc acld hydrazlde- -P- and bromine, Ar is anaphthalene nucleus, each R, is a 153. 54 C fluorocarbon groupcontaining from 1 to 3 carbon Analysis: Calculated for C H F N O z C,39.8; H, atoms and n is l to 3. 3 F 34 N 8 4 Found: c H F7 342; N, 2. Acompound accordlng to claim 1 wherein R, is

i i 3. A com ound accordin to claim 1 wherein n is l.

. P 8 Compounds of the invention of Formula I wherein X 1 (z zaff fl h zph h l Chloride is hydrazmo are obtained by the methods described indetail in Examples 61 and 62 are listed in Table VII.

according to claim 3.

5. A compound of the formula 6. A compound according to claim wherein R,is

cording to claim 6.

wherein X is halogen selected from fluorine chlorine and bromine, Ar isa benzene nucleus, each R, is a fluo- 5 rocarbon group containing from lto 3 carbon atoms 9 and n is 2.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTIONPATENT NO. 3,923,885 Page 1 of 2 DATED December 2, 1975 lN\/ ENTOR(S)Arthur Mendel It is certified that error appears in the above-identifiedpatent and that said Letters Patent are hereby corrected as shown below:

The title should be -PolyfluoroalkoXy-Substituted Aromatic CarboxylicAcids and Derivatives Thereof-- On the title page, column a, line 2:"1,185,096" should be Column 2, line 18: "DX" should be --X- Column 3,lines 20-21: "-(dialky1amino)alkylamines should be deleted Column 3,line 23: "wellknown" should be --we1l-known-- Column I, line 5"3-(2,2,2trifluoroethoxy)-2-naphthoate" should be within the TableColumn I, last line: "propoxy)benzoa" should be --propoxy)benzoate--Column 5, Product of Example 1 should be -methyl 2-(1,l,3-

trihydroperfluoro-npropoxy)benzoate- Column 7, Product of Example 36should be:

--l-(1,l-dihydroperfluoronbutoXy)2-naphthoic acid-- Column 7, Example38, Starting Material should be: I

--n-propyl 2,5-di(1,ldi-

hydroperfluoroisobutoxy)- benzoate UNITED STATES PATENT AND TRADEMARKOFFICE CERTIFICATE OF CORRECTION PATENT NO. ge 2 of 2 DATED December 2,1975 |N\/ E 0R(5) Arthur Mendel It is certified that error appears inthe above-identified patent and that said Letters Patent are herebycorrected as shown below:

Column 7, line 59: 'Irifluoroethoxy) should be --trifluoroethoxy)--Column 9, line 17: delete "benzoic acid" under Starting Material Signedand Sealed this r Fourteenth Day Of September 1976 [SEAL] A ttes r.-

RUTH C. MASON Arresring Officer

1. A COMPOUND OF THE FORMULA
 2. A compound according to claim 1 whereinRf is CF3.
 3. A compound according to claim 1 wherein n is
 1. 4.1-(2,2,2-Trifluoroethoxy)-2-naphthoyl chloride according to claim
 3. 5.A compound of the formula
 6. A compound according to claim 5 wherein Rfis CF3.
 7. 2,5-Di-(2,2,2-trifluoroethoxy)benzoyl chloride according toclaim 6.